The molecular pathogenesis of the Marfan syndrome

The Marfan syndrome (MFS) is an autosomal dominant heritable disorder of co nnective tissue with highly variable clinical manifestations including aort ic dilatation and dissection, ectopia lentis, and a range of skeletal anoma lies. Mutations in the gene for fibrillin-1 (FBN1) cause MFS and other rela ted disorders of connective tissue collectively termed type-1 fibrillino-pa thies. Fibrillin-1 is a main component of the 10- to 12 nm extracellular mi crofibrils that are important for elastogenesis, elasticity, and homeostasi s of elastic fibers, Mutations in fibrillin-1 are hypothesized to exert the ir effects by dominant negative mechanisms, but recent work has also emphas ized the potential role of proteases and disturbances in tissue homeostasis in the pathogenesis of the MFS. This article provides an overview of the c linical aspects of the MFS and current thinking on the pathogenesis of this disorder.